PROJECT SUMMARY Sarcomas are broadly defined as cancers that form in the bone, soft tissue, or connective tissue. While they represent only 1% of all cancers in the United States, sarcomas constitute 12% of all childhood cancers. Typical treatment involves neoadjuvant (presurgical) chemotherapy followed by surgical resection of the tumor; however 5-year survival has not changed in over 40 years. The only clinically accepted indicator of pathologic response and disease-free survival is percent tumor-cell necrosis at time of surgery?there are no established prognostic markers before surgery. Unfortunately, 40-70% of patients have a poor pathologic response and attempts to modify treatment to improve their outcomes have been unsuccessful. The delayed evaluation of treatment response is one potential factor contributing to continued poor outcomes. Given the low response rate and vulnerability of this patient population, developing a prognostic biomarker towards the early identification of poor responders to therapy is crucial to providing individualized, evidence-based changes to treatment, and to improve patient outcomes. Diffuse Optical Spectroscopic Imaging (DOSI) is a non-invasive, functional imagining technique that has been previously implemented to predict pathologic response in patients with breast cancer. Specifically, DOSI combines frequency amplitude modulated near-infrared light and broadband continuous wave light to measure quantitative concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipids. As a functional imaging system, DOSI does not rely on structural changes that take months to manifest, but is sensitive to tumor metabolism and necrosis, thereby providing an early assessment of treatment response. DOSI chemotherapy monitoring, however, is yet to be explored in sarcoma patients, and represents a novel method to determine sarcoma treatment response and personalized treatment strategies.